KpATCC43816 Protein target profile

urocanate hydratase

Accession: VK055_1736

Gene: AIK80356.1 hutU 3D evidence: AlphaFold DB model + ColabFold model Metabolism 1 reaction UniProt A0A1W2IJA7

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Length 562

Pocket druggability (P2Rank · AlphaFold DB model) 0.97

Metabolic reactions 1

Chokepoint Yes

Direct ligand evidence 0 37 total records

Functional annotation 1 EC 4 GO

Target summary

Strong target candidate with converging metabolic, structural and chemical evidence.

Automated synthesis of the evidence currently loaded. Review the underlying records before prioritizing this protein.

Main supporting evidence

Metabolic chokepoint Catalyzes a reaction that is the only producer or consumer of a metabolite in the imported metabolic model. Independent pocket support: P2Rank + FPocket Both predictors report a high-scoring binding site (P2Rank 0.97, FPocket 0.83). Use the 3D pocket comparison to verify whether they identify the same site. Central metabolic position More central than 94.0% of genes in this genome. No isoenzyme backup detected Imported GPR rules do not show an alternative enzyme for the catalyzed reaction set. Review the complete evidence below

Risks to review

Evidence coverage

Core evidence streams are available for this target.

Terms and data sources used on this page

PDB: experimentally determined structures from the Protein Data Bank. These are the strongest structural evidence, but may cover only part of the protein.

AlphaFold DB model: a precomputed predicted structure downloaded from AlphaFold Database/UniProt, not an experiment performed here.

ColabFold model: a predicted structure generated for this workspace; interpret it with coverage and confidence.

pLDDT: confidence score for predicted structures. High values support local geometry; low values mean the region should not drive pocket interpretation.

FPocket / P2Rank: software tools that predict possible ligand-binding pockets on a 3D structure. They are useful screening signals, not experimental validation.

Druggability: a pocket-based estimate of whether a small molecule could bind productively. It does not mean a drug already exists.

PDB ligand: a compound observed in an experimental structure. Direct same-protein records are stronger than homolog-transferred records.

ChEMBL: a public database of measured compound bioactivity. Direct entries are stronger than entries transferred from similar proteins.

ZINC: a purchasable-compound database. Here it marks proposed candidates from chemical similarity, not measured binders.

LigQ / LigQ_2: an internal Target pipeline step that gathers PDB, ChEMBL, and ZINC ligand evidence for each protein.

Off-target: sequence similarity to proteins we prefer not to hit, such as human proteins or beneficial gut microbiome proteins.

DEG: Database of Essential Genes. A match suggests the protein resembles genes known to be essential in other organisms.

Roary / CoreCruncher: pan-genome tools used to decide whether a gene is core across analyzed strains or accessory/strain-specific.

EC / GO: functional annotations: EC describes enzyme reactions; GO describes biological process, molecular function, or cellular component.

KEGG pathway: a curated metabolic route label used here to group reactions imported from the metabolic model.

Chokepoint: a metabolic reaction that is the only producer or consumer of a metabolite in the imported model.

Prioritization evidence

Selectivity, essentiality, structural confidence, conservation, and predicted binding-site evidence.

Off-target risk

Human off-target: Hit
Human identity (%): 34.574 Lower values reduce human off-target concern.
Human E-value: 1.33e-92
Gut microbiome similarity: 3.9% of screened genomes Lower prevalence suggests narrower overlap with the screened gut microbiome.

Essentiality

Essential (DEG): Y
DEG identity (%): 66.362 Higher values support similarity to known essential genes.
DEG E-value: 0.0 Smaller values mean stronger essential-gene similarity.

Structure confidence

ColabFold pLDDT: 97.41 0-100 confidence; >70 supports local structural interpretation.

Binding-site evidence

AlphaFold DB / UniProt model

P2Rank's binding-site probability is the primary druggability signal shown across the app; FPocket's druggability score is shown alongside it for comparison. Both estimate small-molecule pocket quality after applying the curated structure priority — neither is experimental binding evidence. The 3D viewer may show a different loaded structure, so visible pockets can differ.

Druggability (P2Rank) 0.97

Structure A0A1W2IJA7

Pocket Pocket 1

Druggability (FPocket) 0.831

Structure A0A1W2IJA7

Pocket Pocket 13

ColabFold model

P2Rank 0.979 · Pocket 1

FPocket 0.838 · Pocket 23

Core conservation Accessory gene

Roary core

CoreCruncher accessory

Gut microbiome 185 / 4744 genomes with a hit

Prevalence 3.9%

Cross-references

External database identifiers for this protein, its structures, ligands, and metabolic reactions.

Sequence

UniProt A0A1W2IJA7

Pathways

KEGG R02914 BioCyc UROCANATE-HYDRATASE-RXN

Metabolic context

Reactions catalyzed, pathway membership, and centrality in the genome-scale metabolic network.

Explore metabolic network

Attractive metabolic target: catalyzes a producing & consuming chokepoint reaction in Histidine metabolism, no isoenzyme backup detected, more central than 94.0% of genes in this genome.

Relative network centrality 94.0% more central than 94.0% of genes in this genome

Chokepoint Chokepoint gene

Imported from KpATCC43816.sbml · 2026-07-09

Sequence

Primary amino-acid sequence viewer.

MSQSKYRQLDVRAPRGTTLTAKSWLTEAPLRMLMNNLDPDVAENPHELVVYGGIGRAARNWECYDAIVKALKNLESDETLLVQSGKPVGVFKTHENSPRVLIANSNLVPHWATWEHFNELDAKGLAMYGQMTAGSWIYIGSQGIVQGTYETFVEAGRQHYQGSLKGRWVLTAGLGGMGGAQPLAATLAGACSLNIECQQSRIDFRLRTRYVDEQASSLDDALARIKKYTAEGRAISIALCGNAAEIVPELVKRGVRPDVVTDQTSAHDPLHGYLPKGWSWEEYQQKAESDPQGTILAAKRSMADHVQAMLAFHEMGVPTFDYGNNIRQMAQEVGVSNAFDFPGFVPAYIRPLFCRGIGPFRWVALSGDPQDIYKTDAKVKEIIKDDQHLHHWLDMARERISFQGLPARICWVGLEWRQKLGLAFNEMVRSGEVSAPIVIGRDHLDSGSVASPNRETEAMRDGSDAVSDWPLLNALLNTASGATWVSLHHGGGVGMGFSQHSGMVIVCDGTDKAAARIARVLHNDPATGVMRHADAGYDIAIECAAEQGLNLPMVAATQGNAK

Functional annotations

Enzyme classification and Gene Ontology terms linked to this protein.

1 EC 4 GO

Subcellular localization

Localization: Cytoplasmic

Enzyme Commission (EC)

4.2.1.49

Gene Ontology (GO)

GO:0016153 Catalysis of the reaction: 4-imidazolone-5-propanoate + H+ = trans-urocanate + H2O.
GO:0005737 The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
GO:0019556 OBSOLETE. The chemical reactions and pathways resulting in the breakdown of L-histidine into other compounds, including glutamate and formamide.
GO:0019557 OBSOLETE. The chemical reactions and pathways resulting in the breakdown of L-histidine into other compounds, including glutamate and formate.

Sequence domains and features

Domain and signature matches imported from InterPro and related databases.

23 records

Show feature table

Start	End	DB	Term	Name
141	348	Gene3D	G3DSA:3.40.50.10730	Urocanase like domains
141	348	InterPro	IPR038364	Urocanase, central domain superfamily
141	348	FunFam	G3DSA:3.40.50.10730:FF:000001	Urocanate hydratase
441	456	ProSitePatterns	PS01233	Urocanase signature.
441	456	InterPro	IPR023636	Urocanase conserved site
10	553	NCBIfam	TIGR01228	urocanate hydratase
10	553	InterPro	IPR023637	Urocanase
7	554	SUPERFAMILY	SSF111326	Urocanase
7	554	InterPro	IPR036190	Urocanase superfamily
11	137	Pfam	PF17391	Urocanase N-terminal domain
11	137	InterPro	IPR035400	Urocanase, N-terminal domain
1	560	PIRSF	PIRSF001423	Urocanate_hydrat
1	560	InterPro	IPR023637	Urocanase
12	552	Gene3D	G3DSA:3.40.1770.10	Urocanase superfamily
140	348	Pfam	PF01175	Urocanase Rossmann-like domain
140	348	InterPro	IPR035085	Urocanase, Rossmann-like domain
2	555	Hamap	MF_00577	Urocanate hydratase [hutU].
2	555	InterPro	IPR023637	Urocanase
351	545	Pfam	PF17392	Urocanase C-terminal domain
351	545	InterPro	IPR035401	Urocanase, C-terminal domain
211	231	Coils	Coil	Coil
8	558	PANTHER	PTHR12216	UROCANATE HYDRATASE
8	558	InterPro	IPR023637	Urocanase

3D structure

Selected loaded structure. Experimental PDB entries may cover only a portion of the sequence; AlphaFold DB and ColabFold models typically cover the full protein but remain computational predictions.

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Pocket score High Medium Low

How colors and pocket overlays are used

Uniform protein color marks the displayed model as a single molecular object.

Experimental PDB structures may be colored by chain to distinguish subunits or copies present in the file.

Pocket colors and alpha spheres are evidence overlays for predicted binding cavities; they are not alternative protein chains.

'Alpha spheres' is FPocket's own cavity-shape geometry, imported when available and aligned with the loaded structure.

'Pocket atoms'/'Predicted site atoms' show the pocket's residue atoms instead: P2Rank reports residues rather than alpha spheres, and FPocket falls back to this when alpha-sphere geometry is unavailable or doesn't align.

'No pocket geometry' means neither alpha spheres nor residue-position data could be found for that pocket; the layer just highlights the same residues as 'Nearby residues'.

Pocket details Inspect a specific pocket, or open the full viewer

Binding pockets · P2Rank

Druggability (P2Rank): high ≥ 0.5 · medium 0.2–0.49 · low < 0.2

Pocket 1 P2Rank #1

0.97

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Surrounding area

Pocket 2 P2Rank #2

0.315

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Surrounding area

Pocket 3 P2Rank #3

0.174

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Surrounding area

Pocket 4 P2Rank #4

0.044

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Surrounding area

Pocket 5 P2Rank #5

0.038

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Surrounding area

Binding pockets · FPocket

Druggability (FPocket): high ≥ 0.7 · medium 0.4–0.69 · low < 0.4

Pocket 1 FPocket #13

0.831

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Surrounding area

Binding pockets · P2Rank

Druggability (P2Rank): high ≥ 0.5 · medium 0.2–0.49 · low < 0.2

Pocket 1 P2Rank #1

0.979

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Surrounding area

Pocket 2 P2Rank #2

0.277

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Surrounding area

Pocket 3 P2Rank #3

0.141

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Surrounding area

Pocket 4 P2Rank #4

0.014

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Surrounding area

Pocket 5 P2Rank #5

0.009

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Surrounding area

All structural evidence 0 experimental · 2 predicted

Structural evidence

0 + 2

Experimental PDB entries plus predicted AlphaFold DB or ColabFold models. Click Switch to display a different loaded structure in the viewer.

Entry	Method	Resolution	Chain	Coverage	Links	Status
AlphaFold DB AF_A0A1W2IJA7	AlphaFold DB	—	—	full sequence	—	Viewing
ColabFold VK055_1736	ColabFold	—	—	full sequence	—	Loaded

Ligand evidence

Ligands grouped by evidence source. PDB ligands keep the source crystal visible, and loaded crystals can be opened directly in the structure viewer.

37 records

Chemistry signal

Structural ligand evidence is available for this target.

Direct evidence 0 same-protein records

Transferred evidence 2 records from similar proteins

Structural ligands 2 0 loaded crystals

Measured bioactivity 0 direct and transferred ChEMBL records

Proposed compounds 35 similarity-based ZINC candidates

Best available ligand signal

SIN PDB via homolog 118.1 Da · LogP -0.06 · TPSA 74.6 Open detail RCSB PDB

URO PDB via homolog Detail RCSB PDB

ZINC1529497 ZINC proposed compound · Tanimoto 0.615 Detail ZINC

ZINC1531045 ZINC proposed compound · Tanimoto 0.615 Detail ZINC

ZINC1593115 ZINC proposed compound · Tanimoto 0.615 Detail ZINC

Highest-confidence structural evidence: ligands co-crystallized with this exact protein. If the source PDB is loaded in Target, use Open crystal to inspect it in the structure viewer.

No PDB structure with a co-crystallized ligand found for this exact protein.

Structural evidence inferred from similar proteins. The source crystal indicates where the ligand was observed; the UniProt column identifies the homologous protein carrying that ligand.

Ligand	Source crystal	UniProt (homolog)	MW · LogP · TPSA	Lipinski	PAINS	SMILES
SIN RCSB PDB	7JFZ	Q5ZVR1	118.1 Da LogP -0.06 TPSA 74.6	✓ Ro5	✓ Clean	`C(CC(=O)O)C(=O)O`
URO RCSB PDB	7NED	A0A0Q9KFZ4	138.1 Da LogP 0.51 TPSA 66.0	✓ Ro5	✓ Clean	`c1c(nc[nH]1)C=CC(=O)O`

Experimental bioactivity from ChEMBL measured directly on this protein. Score = pchembl (−log Ki/IC₅₀; higher = more potent).

No ChEMBL bioactivity data found for this exact protein.

Bioactivity inferred from similar proteins in ChEMBL. Score = pchembl (−log Ki/IC₅₀; higher = more potent).

No ChEMBL hits found through similar proteins.

Proposed virtual-screening candidates from ZINC. Score = Tanimoto similarity to a known binder (0–1; higher = more similar).

Ligand	Tanimoto	MW · LogP · TPSA	Lipinski	PAINS	SMILES
ZINC1529497 ZINC	0.615	230.3 Da LogP 3.06 TPSA 74.6	✓ Ro5	✓ Clean	`O=C(O)CCCCCCCCCCC(=O)O`
ZINC1531045 ZINC	0.615	202.2 Da LogP 2.28 TPSA 74.6	✓ Ro5	✓ Clean	`O=C(O)CCCCCCCCC(=O)O`
ZINC1593115 ZINC	0.615	216.3 Da LogP 2.67 TPSA 74.6	✓ Ro5	✓ Clean	`O=C(O)CCCCCCCCCC(=O)O`
ZINC1700020 ZINC	0.615	244.3 Da LogP 3.45 TPSA 74.6	✓ Ro5	✓ Clean	`O=C(O)CCCCCCCCCCCC(=O)O`
ZINC3860440 ZINC	0.615	258.4 Da LogP 3.84 TPSA 74.6	✓ Ro5	✓ Clean	`O=C(O)CCCCCCCCCCCCC(=O)O`
ZINC3861298 ZINC	0.615	286.4 Da LogP 4.62 TPSA 74.6	✓ Ro5	✓ Clean	`O=C(O)CCCCCCCCCCCCCCC(=O)O`
ZINC5113062 ZINC	0.615	272.4 Da LogP 4.23 TPSA 74.6	✓ Ro5	✓ Clean	`O=C(O)CCCCCCCCCCCCCC(=O)O`
ZINC13283631 ZINC	0.564	224.3 Da LogP 0.67 TPSA 55.0	✓ Ro5	✓ Clean	`C[N+](C)(C)CCOC(=O)/C=C/c1c[nH]cn1`
ZINC1572706 ZINC	0.563	260.2 Da LogP -1.05 TPSA 132.8	✓ Ro5	✓ Clean	`O=C(O)CCC(=O)NCCNC(=O)CCC(=O)O`
ZINC1703342 ZINC	0.533	202.2 Da LogP 1.07 TPSA 91.7	✓ Ro5	✓ Clean	`O=C(O)CCCC(=O)CCCC(=O)O`
ZINC1728397 ZINC	0.533	233.2 Da LogP -0.29 TPSA 115.1	✓ Ro5	✓ Clean	`O=C(O)CCN(CCC(=O)O)CCC(=O)O`
ZINC2508031 ZINC	0.533	230.3 Da LogP 1.85 TPSA 91.7	✓ Ro5	✓ Clean	`O=C(O)CCCCC(=O)CCCCC(=O)O`
ZINC2517013 ZINC	0.533	250.2 Da LogP 0.89 TPSA 111.9	✓ Ro5	✓ Clean	`O=C(O)CCP(CCC(=O)O)CCC(=O)O`
ZINC1697439 ZINC	0.529	219.5 Da LogP 1.79 TPSA 54.4	✓ Ro5	✓ Clean	`O=C(O)CCC(=O)C(Cl)(Cl)Cl`
ZINC35465466 ZINC	0.529	244.3 Da LogP 2.24 TPSA 91.7	✓ Ro5	✓ Clean	`O=C(O)CCCCCCCC(=O)CCC(=O)O`
ZINC39208104 ZINC	0.529	262.2 Da LogP -0.20 TPSA 127.2	✓ Ro5	✓ Clean	`O=C(O)CCC(=O)OCCOC(=O)CCC(=O)O`
ZINC145743383 ZINC	0.500	266.2 Da LogP 0.77 TPSA 129.0	✓ Ro5	✓ Clean	`O=C(O)CCP(=O)(CCC(=O)O)CCC(=O)O`
ZINC1542984448 ZINC	0.500	470.5 Da LogP 0.07 TPSA 148.4	✓ Ro5	✓ Clean	`O=C(O)CCOCCOCCOCCOCCOCCOCCOCCOCCC(=O)O`
ZINC1586444 ZINC	0.500	210.2 Da LogP -0.65 TPSA 108.7	✓ Ro5	✓ Clean	`O=C(O)CCS(=O)(=O)CCC(=O)O`
ZINC1753095 ZINC	0.500	238.3 Da LogP 1.40 TPSA 74.6	✓ Ro5	✓ Clean	`O=C(O)CCSCCSCCC(=O)O`
ZINC22028383 ZINC	0.500	204.2 Da LogP -0.88 TPSA 98.7	✓ Ro5	✓ Clean	`O=C(O)CCNCCNCCC(=O)O`
ZINC22576322 ZINC	0.500	348.4 Da LogP -0.51 TPSA 155.7	✓ Ro5	✓ Clean	`O=C(O)CCN(CCC(=O)O)CCN(CCC(=O)O)CCC(=O)O`
ZINC26897400 ZINC	0.500	286.4 Da LogP 3.41 TPSA 91.7	✓ Ro5	✓ Clean	`O=C(O)CCCCCCC(=O)CCCCCCC(=O)O`
ZINC3074813 ZINC	0.500	258.3 Da LogP 2.63 TPSA 91.7	✓ Ro5	✓ Clean	`O=C(O)CCCCCC(=O)CCCCCC(=O)O`
ZINC34423725 ZINC	0.500	342.5 Da LogP 4.97 TPSA 91.7	✓ Ro5	✓ Clean	`O=C(O)CCCCCCCCC(=O)CCCCCCCCC(=O)O`
ZINC35977596 ZINC	0.500	294.3 Da LogP 0.00 TPSA 111.5	✓ Ro5	✓ Clean	`O=C(O)CCOCCOCCOCCOCCC(=O)O`
ZINC38682833 ZINC	0.500	286.3 Da LogP -0.61 TPSA 115.2	✓ Ro5	✓ Clean	`O=C(O)CCC(=O)N1CCN(C(=O)CCC(=O)O)CC1`
ZINC39383060 ZINC	0.500	206.2 Da LogP -0.03 TPSA 93.1	✓ Ro5	✓ Clean	`O=C(O)CCOCCOCCC(=O)O`
ZINC39427081 ZINC	0.500	250.2 Da LogP -0.01 TPSA 102.3	✓ Ro5	✓ Clean	`O=C(O)CCOCCOCCOCCC(=O)O`
ZINC4181831 ZINC	0.500	232.2 Da LogP -0.01 TPSA 129.0	✓ Ro5	✓ Clean	`O=C(O)CCC(=O)C(CC(=O)O)CC(=O)O`
ZINC4822898 ZINC	0.500	272.3 Da LogP 3.02 TPSA 91.7	✓ Ro5	✓ Clean	`O=C(O)CCCCCCC(=O)CCCCCC(=O)O`
ZINC4822900 ZINC	0.500	300.4 Da LogP 3.80 TPSA 91.7	✓ Ro5	✓ Clean	`O=C(O)CCCCCCCCC(=O)CCCCCC(=O)O`
ZINC71257127 ZINC	0.500	426.5 Da LogP 0.05 TPSA 139.2	✓ Ro5	✓ Clean	`O=C(O)CCOCCOCCOCCOCCOCCOCCOCCC(=O)O`
ZINC71257128 ZINC	0.500	338.4 Da LogP 0.02 TPSA 120.8	✓ Ro5	✓ Clean	`O=C(O)CCOCCOCCOCCOCCOCCC(=O)O`
ZINC79016464 ZINC	0.500	382.4 Da LogP 0.04 TPSA 130.0	✓ Ro5	✓ Clean	`O=C(O)CCOCCOCCOCCOCCOCCOCCC(=O)O`

PDB and ChEMBL records on this protein are shown in full. ChEMBL records from similar proteins are capped at the top 100 per protein (by pchembl) and ZINC at the top 50 (Tanimoto ≥ 0.5). ADME columns are descriptor-based screening flags, not experimental toxicity results.